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1.
Clin Ter ; 175(4): 252-258, 2024.
Article in English | MEDLINE | ID: mdl-39010810

ABSTRACT

Abstract: The right to live with dignity during the final stages of existence, enshrined in national and supranational Charters of Rights, represents a significant step towards humanizing medicine and is integral to the right to health. Palliative Care, rooted in health, dignity, and therapeutic self-determination, has emerged as a fundamental human right and a moral imperative within health systems. It seeks to alleviate suffering, emphasizing the holistic well-being of patients with life-limiting illnes-ses. This paper provides an analysis of the current situation of Palliative Care in Italy and examines its critical aspects, also in relation to the issues found in other European and non-European countries. In Italy, although laws have been enacted to ensure the provision of Palliative Care, its availability remains inconsistent across different regions. Financial constraints and insufficient support hinder the comprehensive dissemination of these services. Recognizing the significance of Palliative Care, the Catholic Church also endorses its implementation as a response to human suffering and an approach to end-of-life care. Efforts to strengthen Palliative Care are critical to meeting the rising demand and ensuring access to compassionate and dignified care for all individuals in need. Through legislative advancements and adequate resources, Italy can make significant strides in advancing the provision of Palliative Care.


Subject(s)
Human Rights , Palliative Care , Italy , Palliative Care/legislation & jurisprudence , Palliative Care/ethics , Humans , Human Rights/legislation & jurisprudence , Catholicism
2.
ESMO Open ; 9(5): 103461, 2024 May.
Article in English | MEDLINE | ID: mdl-38744102

ABSTRACT

BACKGROUND: Results from the JAVELIN Merkel 200 study led to the approval of avelumab [an anti-programmed death-ligand 1 (PD-L1) antibody] for the treatment of metastatic Merkel cell carcinoma (mMCC) in multiple countries and its inclusion in the treatment guidelines as a preferred or recommended therapy in this setting. Here, we report 4-year follow-up results from the cohort of patients with mMCC who received avelumab as first-line treatment. PATIENTS AND METHODS: In part B of JAVELIN Merkel 200, a single-arm, open-label, phase II study, patients with mMCC who had not received prior systemic therapy for metastatic disease received avelumab 10 mg/kg via intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. In this analysis, long-term overall survival (OS), patient disposition, and subsequent treatment were analyzed. RESULTS: In total, 116 patients received first-line avelumab. At the data cutoff (2 February 2022), the median follow-up was 54.3 months (range 48.0-69.7 months). Seven patients (6.0%) remained on treatment and an additional 21 patients remained in follow-up (18.1%); 72 patients (62.1%) had died. The median OS was 20.3 months [95% confidence interval (CI) 12.4-42.0 months], with a 4-year OS rate of 38% (95% CI 29% to 47%). In patients with PD-L1+ or PD-L1- tumors, the 4-year OS rate was 48% (95% CI 26% to 67%) and 35% (95% CI 25% to 45%), respectively. In total, 48 patients (41.4%) received poststudy anticancer drug therapy, most commonly etoposide (20.7%), carboplatin (19.0%), and avelumab (12.1%). CONCLUSIONS: Avelumab first-line monotherapy in patients with mMCC resulted in meaningful long-term OS, which compared favorably with historical studies of first-line chemotherapy. These results further support the role of avelumab as a standard of care for patients with mMCC.


Subject(s)
Antibodies, Monoclonal, Humanized , Carcinoma, Merkel Cell , Skin Neoplasms , Humans , Carcinoma, Merkel Cell/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Male , Female , Aged , Follow-Up Studies , Middle Aged , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Aged, 80 and over , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents, Immunological/pharmacology , Neoplasm Metastasis , Adult , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/metabolism
3.
Clin Ter ; 175(1): 57-67, 2024.
Article in English | MEDLINE | ID: mdl-38358478

ABSTRACT

Introduction: Historical mistreatment and violence directed toward women's bodies extend to the field of medicine, and obstetric and gynecological practices are not immune to such misconduct. Obstetric violence (OV) refers to actions involving disrespectful, abusive, or coercive treatment directed at pregnant and birthing women. This includes institutional and personal attitudes that lead to the violation of women's autonomy, human rights, and sexual and reproductive health. Despite various international legislative initiatives and recommendations from the World Health Organization (WHO) addressing disrespectful and abusive treatment, OV is still poorly known to Italian public opinion. This study aims to investigate whether the concept of OV has been conversely assimilated in judicial decisions. Materials and methods: A retrospective analysis was conducted to scrutinize judgments in Italy until June 2023 related to OV. The Italian legal database 'De Jure Giuffrè', which collects sentences by various Courts, and the terms 'obstetric' and 'violence' as keywords were used for the research. Results: The full-text revision of the results (n. 41 sentences) al-lowed the selection of 5 eligible contributions covering the following issues: Informed Consent, Kristeller maneuver, Vaginal Birth After Cesarean (VBAC), Acceleration of childbirth without indication, and Episiotomy. The analysis of individual judgments was complemented by an examination of the key issues involved. Conclusions: The reviewed judgments frequently seemed to be grounded in technical aspects and inclined towards a predominant evaluation of childbirth outcomes. However, some encouraging aspects emerged, particularly in terms of attention to the female body, acknowledgment of consequences within the intimate-relational dimension, and a commitment to the principle of self-determination through the provision of free and informed consent. Ensuring the psychophysical well-being of women and unborn children, fostering positive interactions between pregnant women and medical staff, and actively working to reduce the grounds for litigation are among actual emerging priorities in healthcare. In this sense, fundamental elements include the implementation of continuous staff training and education as well as a focus on promoting the self-determination of women, leveraging new technologies for this purpose, and ensuring legal protection of their rights.


Subject(s)
Judgment , Violence , Pregnancy , Female , Humans , Retrospective Studies , Italy
4.
Expert Rev Endocrinol Metab ; 18(5): 387-398, 2023.
Article in English | MEDLINE | ID: mdl-37743651

ABSTRACT

INTRODUCTION: In the treatment scenario of PanNETs-targeted therapies are desired but limited, as rarity and heterogeneity on PanNETs pose limitations to their development. AREAS COVERED: We performed a literature review searching for promising druggable biomarkers and potential treatments to be implemented in the next future. We focused on treatments which have already reached clinical experimentation, although in early phases. Six targets were identified, namely Hsp90, HIFa, HDACs, CDKs, uPAR, and DDR. Even though biological rational is strong, so far reported efficacy outcomes are quite disappointing. The reason of that should be searched in the patients' heterogeneity, lack of biomarker selection, poor knowledge of interfering mechanisms as well as difficulties in patients accrual. Moreover, different ways to assess treatment efficacy should be considered, other than response rate, in light of the more indolent nature of NETs. EXPERT OPINION: Development of targeted treatments in PanNETs is still an uncovered area, far behind other more frequent cancers. Rarity of NETs led to accrual of unselected populations, possibly jeopardizing the drug efficacy. Better patients' selection, both in terms of topography, grading and biomarkers is crucial and will help understanding which role targeted therapies can really play in these tumors.


Subject(s)
Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Neuroendocrine Tumors/drug therapy , Neuroendocrine Tumors/pathology , Treatment Outcome , Biomarkers, Tumor , Patient Selection
5.
Clin Ter ; 174(5): 451-468, 2023.
Article in English | MEDLINE | ID: mdl-37750379

ABSTRACT

Background: Z-Drugs are a category of non-benzodiazepine sedative-hypnotic drugs that include Zolpidem, Zopiclone and Zaleplon. They are all rapidly adsorbed and have a very short half- life, features that make them first-line treatment of insomnia and, in the meantime, first-choice drugs in cases of poisoning for criminal purposes. Z-drugs are frequently use in Drug Facilitated Crime cases (DFC) and Drug Facilitated Sexual Assault (DFSA), namely crimes, robberies, extortion and sexual violence committed after administration of incapacitating substances able to induce sedative-hypnotic effects. In these circumstances, the psychoactive substance is considered as a weapon and constitutes an aggravating circumstance in the criminal act: accordingly, judicial authority legitimates the analytical determination of these substances. Currently, few tests able to detect such drugs are available in daily clinical practice. Aim: The aim of this work is to evaluate the effective utilization of Z-Drugs. Methods: We have analyzed the literature, focusing on cases in which the criminal use of such incapacitating substances has been demonstrated. Relevant scientific articles were identified from PubMed, Cochrane Central, Scopus, Web of Science, Science Direct, EMBASE up to December 2022 using the following keywords: "z-drugs", "drug facilitated crime", "forensic toxicology". The resulting references were screened to exclude duplicates. In addition, non-English papers were excluded. This evaluation left 10 articles (8 case reports and 2 original studies) divided as follows: 1 case report of a DFC (robbery), 6 cases of confirmed DFSA, 3 cases of suspected DFSA, 2 original studies about DFC. Results: The totality of the selected cases showed positive toxicological tests for a single intake of z-drugs. Conclusions: This work has shown the limitations of screening tests currently in use in the emergency rooms. Forensic toxicology tests should be introduced in daily clinical practice.


Subject(s)
Crime Victims , Sex Offenses , Humans , Crime , Hypnotics and Sedatives , Pharmaceutical Preparations , Case Reports as Topic
6.
Cancer Treat Rev ; 117: 102560, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37088017

ABSTRACT

Octreotide and lanreotide are the two somatostatin analogs (SSA) currently available in clinical practice. They have been approved first to control the clinical syndrome (mainly carcinoid syndrome) associated with functioning neuroendocrine tumors (NET) and later for tumor growth control in advanced low/intermediate grade NET. Although evidence regarding their role, especially as antiproliferative therapy, has been increasing over the years some clinical indications remain controversial. Solicited by AIOM (Italian Association of Medical Oncology) a group of clinicians from various specialties, including medical oncology, endocrinology, and gastroenterology, deeply involved in NET for their clinical and research activity, addressed eight open questions, critically reviewing evidence and guidelines and sharing clinical take-home messages. The questions regarded the use of long-acting octreotide and lanreotide in the following settings: functioning and non-functioning NET refractory to label dose, first-line metastatic pulmonary NET, combination with other therapy with an antiproliferative intent, maintenance in NET responding to other therapies, adjuvant treatment, Ki-67-related cut-off, somatostatin receptor imaging, safety, and feasibility. The level of evidence is not absolute for the majority of these clinical contexts, so it is recommended to distinguish routine versus sporadic utilization in very selected cases. Mention of such specific issues by the main European guidelines (ENETS, European Neuroendocrine Tumor Society, and ESMO, European Society for Medical Oncology) was explored and their position reported. However, different clinical decisions on single patients could be made if the case is carefully discussed within a NET-dedicated multidisciplinary team.


Subject(s)
Neuroendocrine Tumors , Octreotide , Humans , Octreotide/therapeutic use , Neuroendocrine Tumors/drug therapy , Somatostatin/therapeutic use , Peptides, Cyclic/therapeutic use
8.
Clin Ter ; 173(3): 235-242, 2022 May 25.
Article in English | MEDLINE | ID: mdl-35612338

ABSTRACT

Abstract: Voluntary interruption of pregnancy (VIP) in Italy is regulated by Law no. 194/1978. Its monitoring is carried out by the VIP Epidemio-logical Surveillance System, which periodically analyses the results of questionnaires compiled by the territorial healthcare structures and sent by each Region. The latest report, covering the years 2019 and 2020, highlights the adequacy of preventive and proactive strategies, an improvement in the quality and effectiveness of the service offered. Furthermore, considering the COVID-19 pandemic, the reorganization of the IVG application guidelines showed a considerable adaptation to the emergency context through measures such as the increase in pharmacological procedures compared to surgical procedures. The interpretation of the data shows that in Italy there is one of the lowest VIP rates in Europe, reflecting the effectiveness of campaigns that promote responsible procreation. Further implementations should be extended to the foreign population, which still shows a medium-high VIP rate. The efficiency of the service offered resulted to be high. The latter was assessed considering the waiting period required for the performance of the VIP procedure. Furthermore, the high percentage of conscientious objectors does not harm the healthcare service. The estimates show an adequate territorial coverage by the authorized structures compared to the female population of fertile age. In conclusion, the central action of planning, organization, and monitoring finds a valid ally in the territorial management entrusted to the Regions. The analyzed report reflects even more margins of efficiency and adequacy when considered within the particular historical context of the pandemic by COVID-19.


Subject(s)
COVID-19 , Pandemics , COVID-19/epidemiology , COVID-19/prevention & control , Delivery of Health Care , Europe , Female , Humans , Italy/epidemiology , Pandemics/prevention & control , Pregnancy
9.
Ann Surg Oncol ; 29(9): 5568-5577, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35583694

ABSTRACT

BACKGROUND: Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date. OBJECTIVE: The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence. PATIENTS AND METHODS: This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) [G1/G2] that underwent R0/R1 surgery (years 2000-2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan-Meier method and risk factor analysis was performed using the Cox regression model. RESULTS: Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (p < 0.01). CONCLUSIONS: Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.


Subject(s)
Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Neoplasm Recurrence, Local/pathology , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/pathology , Prognosis , Retrospective Studies , Risk Factors , Survival Rate
10.
Clin Ter ; 173(1): 1-5, 2022 Feb 07.
Article in English | MEDLINE | ID: mdl-35147638

ABSTRACT

ABSTRACT: Post-traumatic gas gangrene is a rare but potentially life-threa-tening condition due to soft tissues infection by Clostridium species. These anaerobic microaerophile bacteria are highly resistant to external insults related to their ability to produce spores, which can survive on any surface for long periods. Under certain conditions suitable for proliferation (such as in ischemic tissues), bacteria produce many to-xins. In particular, Clostridium perfringens type A represents the most frequent cause of traumatic gas gangrene nowadays. It produces toxins responsible for thrombotic and necrotic phenomena in soft tissues and rapid disease diffusion to muscles. Clinical manifestations usually start as local edema and emphysema but rapidly evolve into a septic state. Prognosis is poor in 20-30% of cases, and death occurs due to multiorgan failure. Because of its rapid evolution, clinical diagnosis is not always obtained, thus determining the need for post-mortem investigation. This case report presents a rare case of fulminant gas gangrene due to Clostridium Perfrigens infection developed after trau-matic injury. Despite the prompt antibiotic administration and surgical intervention on the site of trauma, gas gangrene rapidly evolved into septic shock, leading to the patient's death. Post-mortem investigations were conducted and confirmed multiorgan failure as the cause of death. Cultural analysis was also performed but showed no bacterial growth. Negativity on culture tests should be related to antibiotic administration before blood sampling and bacterial characteristics. In such cases, the correct identification of the cause of death was only possible following a careful and detailed forensic methodological approach.


Subject(s)
Clostridium Infections , Gas Gangrene , Shock, Septic , Clostridium Infections/complications , Clostridium Infections/diagnosis , Clostridium perfringens , Gas Gangrene/diagnosis , Gas Gangrene/etiology , Humans , Necrosis
11.
Expert Opin Drug Saf ; 21(3): 303-310, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34724869

ABSTRACT

INTRODUCTION: Sunitinib still represents a milestone in the treatment for progressive, well-differentiated, advanced panNETs. AREAS COVERED: We performed an evidence reappraisal to critically discuss its safety profile. We included nine studies, five clinical trials and four real-world (RW) studies. Within non-real-world (NRW) studies, diarrhea was the most frequent clinical AE. With regard to G3-4 AEs, fatigue and hypertension were the two most frequent, while neutropenia was the most recurrent hematological one. Considering four real-world trials, hand-foot-syndrome (HFS) was the most frequent clinical any-grade AE of any grade and neutropenia was the most common G3-4. Alongside to the AEs rate, the discontinuation rate of sunitinib due to TRAEs was variable among all the nine selected studies, ranging from 10% to 35% in the NRW setting and from 7% to 31% in the RW setting. Conversely, temporary interruption is an accepted strategy to reduce toxicity, even though not specifically tested in pan-NET. EXPERT OPINION: Till now, sunitinib continues to be one of the main therapeutic options for patients with well differentiated advanced panNETs, potentially covering any line of treatment. Therefore, tolerability plays a crucial role to increase adherence to therapy and maximize QoL.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Sunitinib , Antineoplastic Agents/adverse effects , Carcinoma, Renal Cell/drug therapy , Humans , Kidney Neoplasms/drug therapy , Quality of Life , Receptor Protein-Tyrosine Kinases , Sunitinib/adverse effects
12.
J Endocrinol Invest ; 45(2): 317-325, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34282554

ABSTRACT

PURPOSE: Grade 3 neuroendocrine tumor (NET G3) is a novel pathologic category within gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NENs) but its clinical behavior and therapeutic management still remain challenging. Prognostic and predictive factors aiding NET G3 management are needed. PATIENTS AND METHODS: We performed a retrospective analysis from 2015 to 2020 of all patients with > 20% Ki-67, well-differentiated NETs evaluated within our NEN-dedicated multidisciplinary team. We divided the sample according the timing of NET G3 diagnosis, the radiotracers distribution and Ki-67. We analyzed the correlation between these NET G3 features and clinical outcomes. RESULTS: Among 3238 multidisciplinary discussion reports, we selected 55 patients, 48 from GEP and 7 from an occult GEP origin. In 45 patients, NET G3 diagnosis occurred at the beginning of clinical history (upfront-NET G3), whereas in 10, during the NET G1-G2 clinical history (late-NET G3). Patients with ≤ 30% (34/55) vs. > 30% Ki-67 (21/55) had a better overall survival (OS) (p = 0.042); patients with a homogeneous vs. inhomogeneous/negative 68Gallium(68Ga)-DOTA-Peptide Positron Emission Tomography (PET)/computed tomography (CT) showed a trend to a better OS, and a significant better progression-free survival (PFS) (p = 0.033). A better OS was observed for negative/inhomogeneous vs. homogeneous 18-fluorodeoxyglucose (18FDG)-PET/CT (p = 0.027). A trend to a better OS was reported in late- vs. upfront-NET G3, while the latter showed a significantly better response rate (RR) (p = 0.048). CONCLUSION: Our findings suggested that Ki-67 cutoff, functional imaging and the timing to NET G3 diagnosis may help clinicians in more accurate selection of NET G3 management. Prospective studies are needed.


Subject(s)
Early Detection of Cancer/methods , Intestinal Neoplasms , Ki-67 Antigen/analysis , Neuroendocrine Tumors , Pancreatic Neoplasms , Positron Emission Tomography Computed Tomography , Stomach Neoplasms , Female , Fluorodeoxyglucose F18/pharmacology , Humans , Immunohistochemistry , Intestinal Neoplasms/diagnosis , Intestinal Neoplasms/metabolism , Intestinal Neoplasms/mortality , Intestinal Neoplasms/therapy , Italy/epidemiology , Male , Middle Aged , Neoplasm Grading , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/metabolism , Neuroendocrine Tumors/mortality , Neuroendocrine Tumors/therapy , Organometallic Compounds/pharmacology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/therapy , Patient Selection , Positron Emission Tomography Computed Tomography/methods , Positron Emission Tomography Computed Tomography/statistics & numerical data , Prognosis , Radiopharmaceuticals/pharmacology , Retrospective Studies , Stomach Neoplasms/diagnosis , Stomach Neoplasms/metabolism , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Survival Analysis
13.
Clin Ter ; 172(5): 414-419, 2021 Sep 29.
Article in English | MEDLINE | ID: mdl-34625770

ABSTRACT

ABSTRACT: The Coronavirus Disease-19 (Covid-19) pandemic, in the last year, has resulted in a significant number of infections and deaths among nursing homes' residents. This phenomenon has set up the necessity to subject these patients, often suffering from mental disabilities to a vaccination against Covid-19. However, vaccination has long been the subject of public atten-tion, being regulated differently in many European countries. In Italy, the Ministry of Health has given priority, vaccination-wise, to health facilities' patients. The government has regulated through-law no. 1 of January 5, 2021, art. 5, the manifestation of consent to be Covid-19 vac-cinated in incapacitated subjects admitted to assisted health facilities. This rule arose from the need to protect fragile individuals as well as providing real dispositions for the involved health professionals. Nursing homes' elderly guests could be divided into four catego-ries: a) subjects capable to express their will (affected by physical problems); b) subjects who, due to varying degrees of incapacitation, have their own legal guardian, curator or support administrator, ap-pointed in accordance with the law; c) incapacitated subjects without legal representatives d) subjects who, pursuant to law no. 219/2017, have appointed their own trustee. This paper provides for a clear exemplification of all the possible scenarios identified by the Italian law no.1/2021.


Subject(s)
COVID-19 , Aged , Humans , Italy/epidemiology , Nursing Homes , SARS-CoV-2 , Vaccination
15.
Clin Ter ; 172(4): 253-255, 2021 Jul 05.
Article in English | MEDLINE | ID: mdl-34247204

ABSTRACT

ABSTRACT: Law No 40/2004 regulates in Italy the matter of medically assisted procreation (MAP). Recently, the Tribunal of Capua Vetere expressed its position on the subject of informed consent in a case of MAP. In the specific case, a couple entered the preliminary stages of the PMA procedures, carrying out the fertilization of the ovum and the embryo production. Afterwards, the couple separated and the man denied consent to the continuation of the MAP. The woman, willing to proceed with the implantation, the woman made an urgent judicial appeal, obtaining the judge's permission to transfer the embryo to the uterus. This paper analyses the different bioethical positions on MAP's informed consent. In fact, on the one hand, the paper highlight what is set out in Law 219/2017 which provides for the possibility of the patient to revoke at any time the consent to the treatment given. On the other hand, it should be noted that Law 40/2004, willing to protect the embryo, establishes the irrevocability of the position of parental consent after fertilization. The judgment in question seems to favour this latter position, placing itself in the protection of the cryopreserved embryo and recall-ing the principle of entrustment following the fertilization of the egg. Nevertheless, the matter is controversial a consistent amount of legal developments are expected to arise in the next future.


Subject(s)
Embryo Implantation , Informed Consent/ethics , Informed Consent/legislation & jurisprudence , Informed Consent/standards , Reproductive Techniques, Assisted/ethics , Reproductive Techniques, Assisted/legislation & jurisprudence , Reproductive Techniques, Assisted/standards , Adult , Divorce/legislation & jurisprudence , Embryo, Mammalian , Female , Humans , Italy , Male , Parents
16.
Cancer Treat Rev ; 99: 102261, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34332293

ABSTRACT

BACKGROUND: Temozolomide (TEM) is an active treatment in metastatic neuroendocrine tumors (NETs). Patients affected by glioblastoma multiforme or advanced melanoma treated with TEM who have deficiency of O6-methylguanine DNA methyltransferase (MGMT) have a better responses and survival. However, the predictive role of MGMT in patients with NETs treated with TEM is still debated. METHODS: We conducted a systematic review of the literature and meta-analysis, based on PRISMA methodology, searching in the main databases (PubMed, Embase, Scopus, Web of Science, Cochrane Library and clinical trial.gov) and the proceedings of the main international congresses, until April 26, 2021. RESULTS: Twelve out of 616 articles were selected for our analysis, regarding a total of 858 NET patients treated with TEM-based chemotherapy. The status of MGMT had been tested in 513 (60%) patients, using various methods. The pooled overall response rate (ORR) was higher in MGMT-deficient compared with MGMT-proficient NETs, with a risk difference of 0.31 (95% confidence interval, CI: 0.13-0.50; p < 0.001; I2: 73%) and risk ratio of 2.29 (95% CI: 1.34-3.91; p < 0.001; I2: 55%). The pooled progression free survival (PFS) (hazard ratio, HR = 0.56; 95% CI: 0.43-0.74; p < 0.001) and overall survival (OS) (HR = 0.41; 95% CI: 0.20-0.62; p = 0.011) were longer in MGMT-deficient versus MGMT-proficient NETs. CONCLUSIONS: Our meta-analysis suggested that MGMT status may be predictive of TEM efficacy. However, due to the high heterogeneity of the evaluated studies the risk of biases should be considered. On this hypothesis future homogeneous prospective studies are warranted.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , DNA Modification Methylases/deficiency , DNA Repair Enzymes/deficiency , Neuroendocrine Tumors/drug therapy , Neuroendocrine Tumors/enzymology , Tumor Suppressor Proteins/deficiency , Clinical Trials, Phase II as Topic , DNA Modification Methylases/metabolism , DNA Repair Enzymes/metabolism , Humans , Progression-Free Survival , Randomized Controlled Trials as Topic , Temozolomide/administration & dosage , Tumor Suppressor Proteins/metabolism
18.
Lung Cancer ; 148: 149-158, 2020 10.
Article in English | MEDLINE | ID: mdl-32916569

ABSTRACT

Highly proliferative lung carcinoids (HPLC) have been recently reported but information about this subset remains scarce. OBJECTIVES: Clinical and pathological data of 630 patients with lung carcinoids (LC) referred to Gustave Roussy Institute (GR) and European Institute of Oncology (IEO) were retrospectively reviewed to select HPLC and analyze their frequency, behavior and compare their outcome to conventional LC with Ki-67 ≤ 20 % and mitotic count (MC)≤10/2 mm2. MATERIALS AND METHODS: Selection criteria were: diagnosis of LC confirmed by local pathologist, and available clinical and follow-up data. Patients with Ki-67 > 20 % and/or MC > 10/ 2 mm2 in primary or metastatic specimens were identified as HPLC. RESULTS: 30/514 patients (6%) met the selection criteria of HPLC. Based on primary tumor evaluation, 22/25 (88 %) were classified as atypical carcinoids (AC). Median MC was 4.5/2 mm2 (1-11) 6/2 mm2 (3-15) in primary tumors and metastasis, respectively. Median Ki-67 was respectively 23 % (15-65) and 25 % (8-60). Recurrence rate was 66 % (12/18) in HPLC and 9 % (33/352) in conventional LC. Median RFS was 24 (10-NR) months in HPLC, 288 (141-NR) months in LC with Ki-67 index≤5 % and NR (148-NR) months in LC with Ki-67 6-20% (p < 001). Median OS was 203 (83-NR) months in LC with Ki-67 index≤5%, 101 (79-NR) months in LC with Ki-67 index 6-20 % and 53 (39-NR) months in HPLC (p = 002). Among 20 metastatic patients with HPLC, median PFS under platinum-based chemotherapy, everolimus, alkylating-based chemotherapy, FOLFOX and PRRT was 5.1 (95 % CI 0.7-9.4), 12.1(95 %CI 0.3-24), 6.8 (95 % CI 0-14.9), 10.2 (95 % CI 0.4-19.9) and 14.2 months (95 % CI 0-30) respectively. Best response was stable disease (SD) under platinum-based chemotherapy and partial response (PR) under alkylating-based chemotherapy and FOLFOX. CONCLUSION: This study confirms the existence and rarity of HPLC. Their characteristics and clinical behavior are more similar to LC rather than neuroendocrine carcinomas (NECs), suggesting that this entity could be managed accordingly.


Subject(s)
Carcinoid Tumor , Carcinoma, Neuroendocrine , Lung Neoplasms , Neuroendocrine Tumors , Carcinoid Tumor/diagnosis , Humans , Ki-67 Antigen , Lung , Lung Neoplasms/diagnosis , Neoplasm Recurrence, Local , Retrospective Studies
19.
Endocrine ; 70(1): 6-10, 2020 10.
Article in English | MEDLINE | ID: mdl-32681385

ABSTRACT

Primary neuroendocrine tumors of the thymus are extremely rare. In patients with advanced disease, tumor growth control, and sometimes also syndrome control are the main goals of systemic therapy. Unfortunately, no standard therapies are available in clinical practice; therefore, clinical studies are strongly recommended. Axitinib (AXI) is a tyrosine kinase inhibitor, currently under investigation in an international phase II/III trial including thymic neuroendocrine tumors. Over the past 5 months, the entire world has been facing a devastating medical emergency brought about by a pandemic due to a novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China, in late 2019. Since then, health professionals have been expending all their efforts on trying to provide the best available treatments for patients involved. Patients with cancer, especially those with thoracic involvement, are at higher risk of coronavirus disease 19 (COVID-19) and its complications because of their immunosuppressive status caused by the cancer and the anticancer therapies. As it remains unclear how to optimally manage such patients, we wished to report our experience with a patient with a metastatic neuroendocrine tumor of the thymus infected with SARS-CoV-2 in the hope that it may provide some insights and reflections on the management of cancer patients during this challenging time in our history.


Subject(s)
Betacoronavirus , Carcinoid Tumor/drug therapy , Coronavirus Infections/epidemiology , Neuroendocrine Tumors/drug therapy , Pneumonia, Viral/epidemiology , Thymus Neoplasms/drug therapy , Aged , Axitinib/adverse effects , Axitinib/therapeutic use , Azithromycin/therapeutic use , COVID-19 , Carcinoid Tumor/epidemiology , Comorbidity , Coronavirus Infections/diagnosis , Humans , Hydroxychloroquine/therapeutic use , Italy/epidemiology , Male , Neuroendocrine Tumors/epidemiology , Pandemics , Pneumonia, Viral/diagnosis , Protein-Tyrosine Kinases/antagonists & inhibitors , Randomized Controlled Trials as Topic , SARS-CoV-2 , Thymus Neoplasms/epidemiology , Tomography, X-Ray Computed , Treatment Outcome
20.
Clin Ter ; 171(2): e94-e96, 2020.
Article in English | MEDLINE | ID: mdl-32141477

ABSTRACT

End-of-life decisions are an emergent issue for bioethical debates and practical concerns among health professionals. On December 2017, Italy enacted a new law named "Rules about informed consent and advance directives", which promotes the relationship of care in a fiduciary sense through the implementation of a correct and exhaustive information. It is also prescribed to record in writing all the patients' decisions about consent or refusal. Furthermore, the law explicitly forbids unreasonable therapeutic obstinacy for terminal patient, legitimizing deep palliative sedation. Finally, the law establishes the use of "advance directives" as a written document by which adults and capable people can express their wishes regarding health treatments and diagnostic tests in anticipation of a possible future incapacity. The law provides that doctors must comply with these directives, unless they appear clearly incongruous or not corresponding to the patient's current clinical condition.


Subject(s)
Advance Directives/legislation & jurisprudence , Informed Consent/legislation & jurisprudence , Terminal Care/legislation & jurisprudence , Adult , Decision Making , Humans , Italy
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